A Room-Temperature Rh-Catalyzed Kinetic Resolution Pathway for Expedient Access to P‑Stereogenic Cyclic Phosphinates.

Area of Science:

• Organic Chemistry
• Asymmetric Catalysis
• Organophosphorus Chemistry

Background:

• P-stereogenic heterocycles are crucial in pharmaceuticals and catalysis.
• Existing synthetic methods, like desymmetrization and C-P cross-coupling, have limitations.
• Efficient and versatile synthesis of these scaffolds is highly sought after.

Purpose of the Study:

• To develop a novel, room-temperature method for enantioselective synthesis of P-stereogenic five-membered heterocycles.
• To explore the utility of rhodium-catalyzed ring-closing hydrofunctionalization for constructing these valuable structures.
• To provide a versatile platform for generating diverse chiral building blocks.

Main Methods:

• Room temperature rhodium-catalyzed enantioselective ring-closing hydrofunctionalization of alkynylphosphinates.
• Utilized DFT calculations to elucidate the reaction mechanism, particularly the role of phenolic additives.
• Investigated the scope and limitations of the reaction with various substituents on phosphorus and the alkyne.

Main Results:

• Successfully synthesized kinetically favored, nonarene-fused P-stereogenic five-membered rings.
• Demonstrated the critical role of phenolic additives in accelerating P-H bond activation via proximal ligation.
• Showcased the method's tolerance for diverse substituents, yielding valuable chiral building blocks.

Conclusions:

• The developed rhodium-catalyzed hydrofunctionalization offers an efficient and versatile route to P-stereogenic heterocycles.
• The mechanistic insights highlight the importance of additive ligation for catalytic efficiency.
• This methodology provides a valuable platform for designing novel pharmaceuticals and chiral ligands.